The thyroid & me & E.

INTRODUCTION

E. is a teenager and a sort of grand niece. She has a small goitre (a swelling in the neck caused by an enlarged thyroid gland). She has had it for some time and I was told that the cause is Hashimoto’s disease – an autoimmune disease of the thyroid gland, whereby thyroid hormone production is compromised. I don’t have a goitre but I have been taking thyroid hormone replacement for a few years. There are both similarities and differences between the thyroid pathology that is affecting E. and myself so perhaps a review of the subject might be useful. I am out of date with what I learned at Medical School and during my own clinical practice, but my starting point will be to first review my own notes and text books and not go looking at Wikipedia and the web for immediate answers.

I will concentrate on the thyroid gland and its production of thyroid hormones. The gland also produces another hormone, called calcitonin (which is involved with calcium metabolism) but I will not talk about it here. It is also worth saying that there are four small parathyroid glands that exist very close to the thyroid gland and which have very different functions. Their only relevance here is to be aware that when there is surgery to the thyroid gland it is vital that the parathyroid glands are not damaged in the process.

THE THYROID HORMONES, IODINE AND SELENIUM

There are two basic thyroid hormones made by the thyroid – Thyroxine (called T4 because it contains 4 iodide molecules) and Triiodothyronine (called T3 because it contains 3 iodide molecules). Iodine is necessary for the creation of both T3 and T4 and the element selenium is needed for the conversion of T4 to T3. The thyroid is the only organ in the body that contains significant amounts of iodine, which is an element obtained in the diet. Some iodine is secreted by the breast and there is some evidence to show that iodine deficiency predisposes people to an increased risk of breast cancer. Iodine is also being trialed to treat fibrocystic breast disease. Many parts of the world are deficient in iodine (particularly remote mountainous regions or areas where there are calciferous rocks or where there has been glaciation). In much of the developed world iodine deficiency has been addressed by the addition of iodine to salt. Goitres, diminished intelligence and cretinism are all found in areas where iodine deficiency is endemic.

The thyroid produces much more T4 than T3 but when the T4 reaches its target organs it is converted into T3 thus making T3 the “active ingredient”. The secretion of thyroid hormones by the gland is primarily regulated by the production of TSH (Thyroid Stimulating Hormone) from the Pituitary gland, which itself is regulated by the production of TRH (Thyroid Regulating Hormone/Thyrotropin Releasing Hormone) from the hypothalamus (a vital part of the brain close to the pituitary and especially involved in regulation of hormones and the autonomic nervous system). Low levels of thyroid hormones, for whatever reason, usually lead to raised levels of TSH in the blood.

Both T3 and T4 levels can be measured to assess the patient’s production of them but measurement of TSH levels is equally vital since high levels of TSH indicate that the thyroid gland is underperforming and needs to be stimulated because it is struggling to produce enough thyroid hormone – as detected by the hypothalamus and pituitary. Normal serum TSH levels are 0.4-4.0 mIU/L (or 0.5-3.0 mIU/L if the patient is actively undergoing replacement therapy).

As has been outlined, the role of iodine (and probably selenium as well) is very important and adequate dietary iodine is needed to make sufficient T4 and T3. Some iodine is freely available but about 99.95% of iodine is bound normally to plasma proteins in a nearly constant ratio so that measurement of PBI (protein bound iodine) can give a useful interpretable amount; the range for serum PBI in healthy patients is 4.0-7.5 mcg/100ml. This is a useful, but not complete, test since other factors can affect iodine binding.  In modern laboratories both free and bound T4 and T3 can be measured. The normal ranges for adults are: Total T4 = 5.0-12 mcg/dL; Free T4 = 1.0-3.0 ng/dL; Total T3 = 80-190 mcg/dL; Free T3 = 0.25-0.65 ng/dL. Radioiodine uptake of I132 or I131 can also be used to help with diagnosis and to differentiate between Primary (high TSH) and Secondary (low TSH) hypothyroidism.

Sometimes there can be adequate dietary iodine but if it gets bound to other substances (known as goitrogens) then inadequate amounts of iodine actually reach the thyroid. Goitrogens include the inorganic ions perchlorate, pertechnetate, thiocyanate and nitrate as well as the drugs phenylbutazone, the sulphonamides and lithium. They are usually ingested in medications for other diseases or if taken by a pregnant mother they can affect the foetus inside her.

THYROID STATUS

Overproduction of thyroid hormones leads to the condition known as hyperthyroidism. Underproduction leads to the condition known as hypothyroidism. A person who appears to have normal production is called euthyroid but note that a person can be clinically euthyroid but sub-clinically hypothyroid or hyperthyroid! Sub-clinical hypothyroidism means that the person feels and appears to be normal, but they have blood tests, notably a raised TSH level, indicating that their thyroid is struggling to produce enough hormone. Sub-clinical hyperthyroidism also occurs in clinically euthyroid patients but who have lower than normal TSH levels. The presence or absence of a goitre (an abnormal swelling of the thyroid) can occur regardless of the thyroid hormone status. The actual appearance and feel of a swollen thyroid may indicate a specific pathology.

  • HYPOTHYROIDISM (Under production of thyroid hormone).

The predominant clinical features arise largely from a reduced metabolic rate, which may fall to 40% of normal in severe cases. The symptoms are insidious and thus often missed for some time but generally consist of undue tiredness, weakness, lethargy, increasing sensitivity to cold, hoarseness, a general slowing of activity, increase in weight, constipation, muscle cramps and menorrhagia (excessively heavy periods). Neurologically there may be impairment of memory, depression, slowness of comprehension and eventually a descent into coma (the “myxoedema madness” first described by Dr Richard Asher).

As the disease progresses, deposits of mucin in the tissues alter the appearance and this phenomenon is known as myxoedema. The face becomes puffy with a thickened tongue and the hair thick and coarse. Infiltration of the vocal cords causes hoarseness and infiltration of the inner ear causes deafness. The heart becomes enlarged and the plasma lipids change for the worse increasing all the risks associated with ischaemic and embolic disease. Carpal tunnel syndrome is common. Microcytic (small red cells) iron deficiency anaemia may be caused by menorrhagia and macrocytic (large red cells) anaemia may also present because of an associated pernicious anaemia, which affects 10% of cases.

Hypothyroidism may or may not be accompanied by goitre. Most, not accompanied by a goitre, seem to arise without a cause though they are probably examples of an auto-immune disease and IgG antithyroid antibodies can be demonstrated in many cases. Hypothyroidism can also be caused by radioactive Iodine therapy or following thyroidectomy for the treatment of hyperthyroidism.

Hypothyroidism with a goitre most commonly occurs where simple goitre is endemic as a result of insufficient intake of iodine. Other causes are the ingestion of goitrogens (which interfere with the synthesis of thyroid hormones) or by infiltration of the gland by cancer cells and also occasionally because of primary disorders of the pituitary gland.

Juvenile hypothyroidism is most commonly associated with autoimmunity (as in Hashimoto’s disease) but can also be due to congenital under-development (even absence) of the thyroid, which may only become apparent when the need for extra thyroid hormone appears during later childhood and adolescence. Just as in adults the onset may be slow and insidious and many of the features are the same as in adults. Growth may be retarded, and the bone epiphyses may be fragmented. Blunting of intellectual development may become apparent during school years.

Congenital hypothyroidism can be caused by (a) rare inborn errors of metabolism (b) in areas of endemic goitre and (c) when the mother has been taking anti-thyroid or iodide medications during pregnancy. Foetal and neonatal hypothyroidism can have severe effects leading to cretinism, which can be either immediately obvious after birth or missed for some time.

  • HYPERTHYROIDISM (over production of thyroid hormone).

This is a group of disorders that involve excessive synthesis and secretion of the thyroid hormones T3 and/or T4. The raised levels lead to a hypermetabolic state with wasting, tachycardia, palpitations, irritability, sweating and heat intolerance. Part of this syndrome is due to an increased stimulation of the sympathetic nervous system with excessive outpouring of adrenalin and associated neurotransmitters. The most severe manifestations are called thyrotoxicosis, when there are toxic effects, which may need emergency intervention. There are four main forms: (a) diffuse toxic goitre (Grave’s disease), (b) toxic multinodular goitre (Plummer’s disease) (c) toxic adenoma along with (d) subacute thyroiditis.

The thyroid normally contains a large supply of its preformed hormones kept in its follicular lumen. These are released in response to TSH but also to LATS (Long Acting Thyroid Stimulator) which is an autoimmune immunoglobulin with TSH-like actions. LATS (and other similar autoimmune antibodies) may be raised is some forms of hyperthyroidism. It is the excess of free and not bound levels of T3/T4 that gives rise to the symptoms of hyperthyroidism. Thus, any process that causes an increase in the peripheral circulation of unbound thyroid hormone can cause thyrotoxicosis. Regardless of the aetiology the result is an increase in the basal metabolic rate with many of the signs and symptoms resembling a state of catecholamine excess. Adrenergic blockade may be useful in management of toxic effects.

Thyrotoxicosis is marked by suppressed TSH levels (unless the pituitary is secreting excessive amounts of TSH due to a tumour) and elevated T3 and T4 levels. Subclinical hyperthyroidism is still marked by suppressed TSH levels though the T3 and T4 levels may be normal. There are two main tests for autoantibodies: anti-TPO (anti-thyroid peroxidase) and TSab (thyroid stimulating antibody) also known as TSI (thyroid stimulating immunoglobulin) or LATS (long-acting thyroid stimulator).

In Graves disease, raised levels of LATS or other stimulatory immunoglobulins provide continuous stimulation of the thyroid as well as increased iodine uptake, protein synthesis and thyroid gland growth. An associated ophthalmopathy is a common accompaniment (exaggerated in cigarette smokers) and in which the eyeballs are pushed forward by tissue behind the eye. The autoimmune disorders found in both hyperthyroid Grave’s Disease and hypothyroid Hashimoto’s disease have a genetic correlation, with clusters occurring in families.

When subjects who live in areas where there is endemic iodine deficiency move to areas where there is sufficient iodine then hyperthyroidism can also result.

Toxic multinodular goitre and toxic adenoma have low or absent anti-TPO and TSab levels.

There are three mainstays of treatment for hyperthyroidism: (a) antithyroid medications such as methimazole, (b) radioactive iodine treatment and (c) thyroidectomy, which is reserved for special circumstances such as severe hyperthyroidism in children, some pregnant women and those with very large goitres or severe ophthalmopathy.

Hyperthyroidism from toxic multinodular goitre and toxic adenoma are permanent but may become euthyroid (normal levels) following treatment. Patients with Grave’s disease may eventually become hypothyroid.

Long-standing hyperthyroidism can result in left ventricular thickening and the risk of heart failure as well as excessive bone resorption and osteoporosis.

  • THYROIDITIS (an inflammation or infection of the thyroid).

Chronic forms (a. Diffuse goitrous also known as the lympadenoid goitre of Hashimoto’s disease, b. Focal forms in association with hyperthyroidism or other goitres & c. Diffuse atrophic which can be mild or severe (primary hypothyroidism).
Subacute (De Quervain’s viral thyroiditis)
Acute forms (Bacterial infection)
Invasive fibrous (Riedel’s thyroiditis)

Chronic diseases such as tuberculosis, sarcoid and syphilitic gummata rarely involve the thyroid gland so the term chronic thyroiditis usually refers to the autoimmune thyroiditis known as Hashmimoto’s disease.

There exist other known organ-specific autoimmune diseases such as Pernicious anaemia, Addison’s disease, Type I Diabetes and Multiple Sclerosis. In Hashimoto’s disease there is lymphocytic infiltration and fibrosis with eventual atrophy of the thyroid which then ceases to fulfil its physiological function. This process is accompanied by the presence in the blood of organ-specific antibodies. It is the intense chronic inflammation and fibrosis that accounts for the goitre. The thyroid is almost uniformly enlarged, smooth, lobulated and firm and it is possible that the trachea and oesophagus may become compressed. The changes are seen at all ages and in both sexes but typically the patient is a middle-aged female with a rubbery diffuse goitre. Patients may be either euthyroid or hypothyroid but thyroid function tests may show evidence of impaired thyroid reserve with a raised plasma TSH.

If the patient with Hashimoto’s has a large goitre, an initial short course of prednisolone often rapidly reduces its size. However, most patients are treated with thyroxine in doses of 0.2-0.3 mg/day and appropriately less in Children. The reduction in size is often slow. When a patient with a large goitre fails to respond or if there are pressure effects on adjacent organs then thyroidectomy may be indicated.

Sub-acute viral thyroiditis is a usually a self-limiting process lasting from months to a couple of years, typically in a young or middle-aged female. The initial goitre is usually of rapid onset and associated with pain. The patient is usually euthyroid.

Acute bacterial thyroiditis is rare and usually spreads from an adjacent infected area.

Invasive Fibrous thyroiditis (Riedel’s struma or woody thyroid) is a rare disorder of unknown origin that can spread into adjacent tissues causing localised compression and discomfort. No medications seem to be effective and excision may be necessary to prevent local complications.

  • MISCELLANEOUS GOITRES

Goitrogen induced goitres are caused by the ingestion of substances that inhibit thyroid hormone synthesis. A simple goitre is defined as one that appears when the other types have been excluded. They may be endemic or sporadic and are either diffuse or nodular. Most are due to a dietary insufficiency of iodine. The requirements for iodine are increased both by goitrogens and by stress and a high calcium intake also seems to have a goitrogenic effect as does drinking polluted water. Rare anomalies such as cows eating too much kale can create milk that is high in thiocyanate and create a local epidemic of goitres in those who have drunk the milk.

Dietary intake of iodine should not be below the recommended intake of 150 mcg per day and this may be insufficient with the additional demands of adolescence and pregnancy.

A simple goitre has hyperplasia of tall columnar epithelial cells resulting in a uniformly enlarged thyroid and is the type of goitre often seen in children and younger adults. Such goitres can go through alternating periods of expansion and contraction such that eventually the thyroid becomes non-uniform and nodular.

The last group of goitres to mention include both benign and malignant neoplasms about which I don’t intend to write about here.

SUMMARY

I have been prompted to review this topic for myself following E’s recent infection of Herpes Zoster affecting her 7th and 8th cranial nerves. I had thought she had a Bell’s palsy of the 7th nerve but did not know about the small rash and a small degree of hearing loss. In the course of investigations she was discovered to have anaemia. The diagnosis of her Hashimoto’s disease also resurfaced and thus also whether management of it should be changed.

E. may still have unresolved questions that may not have been adequately answered. If so, I hope that this résumé may be of some help to her (or similar sufferers) if only to be able to help to pose any questions more effectively. This is not my field of expertise, though I do still have access to some doctors (whom I have a good opinion about) and probably I should talk to them.

In the first place it would be helpful to know that a diagnosis of Hashimoto’s disease is accurate. I believe that the diagnosis is primarily reliant on the detection of specific autoimmune antibodies, so this would need to be confirmed.

In the second place it is necessary to know how hard the thyroid is having to work to provide adequate amounts of thyroid hormones. The actual levels can be measured but the TSH level is also important. E. appears to me to be clinically euthyroid but if the TSH levels are above normal the question arises as to whether she should start taking thyroxine replacement therapy or not. I will return to this later.

In the third place is the presence of anaemia for which she is being treated with iron and a wide-spectrum of B vitamins including oral Vitamin B12. It is very important that the cause of this anaemia is correctly diagnosed. Simple iron deficiency anaemia is seldom due to a lack of intake of iron and is commonly due to excessive blood loss. If she is anaemic because of vitamin B12 deficiency she will obviously need enough iron to allow the new cells to form properly but any underlying pathology (such as in pernicious anaemia stemming from an autoimmune attack on part of her stomach which then prevents the normal absorption of vitamin B12) should to be taken account of and she should be given adequate amounts of vitamin B12 and folate. Vitamin B12 is necessary for more than red blood cell production. Lack of it can affect both DNA synthesis and the normal development of the nervous system. Lack of vitamin B12 and folate during pregnancy can lead to “neural tube defects” in the embryo which can result in spina bifida.

TO TREAT OR NOT TO TREAT SUB-CLINICAL HYPOTHYROIDISM

E. and I both seem to be clinically euthyroid (lacking symptoms of under or over production of hormone). I am, however, definitely sub-clinically hypothyroid because I have high levels of TSH circulating in my body. When this was first diagnosed (my nurse just took a blood sample during a routine check) I thought little about it because I knew that I was clinically euthyroid; I felt absolutely normal. Some knowledgeable doctor friends from England told me I was mad and that I should start taking thyroxine medication. For a long time I ignored them – but not any more.

Thyroid hormones are essential for normal health. They are especially important during various stages of development, notably during pregnancy and adolescence. Possibly I have enough T3 and T4 in my body but the fact that my pituitary is having to pour out excessive amounts of TSH is not normal. What is not clear is whether the over production of these stimulating hormones from my hypothalamus and pituitary could be having effects elsewhere in my body. The whole endocrine system (and indeed the whole neurological system) is so very interlinked that it is unlikely that any part of it should ever be considered in isolation.

In recent times I, myself, have noticed a loss of libido but I had put this down to the normal ageing process. Perhaps it could actually be related to my thyroid function because I now read that adequate thyroid function is necessary for normal potency and libido in both men and women.

I can’t answer for, or advise, E. on whether to start taking thyroxine or not. I just don’t know but first of all I think the diagnosis of Hashimoto’s needs to be confirmed and for her to also know, more precisely, what her thyroid hormone and TSH levels are. I do think she should review any thinking about both vitamin B12 and thyroxine if she is ever contemplating becoming pregnant.

I, unlike E., have no goitre and am nearer the end of my life than its beginning so aspects of my hypothyroidism are of much less importance. I have only just realised that I, myself, don’t have an accurate diagnosis so I will be doing more blood tests at the next visit to my nurse to determine the actual cause and indeed whether or not I have late onset Hashimoto’s disease.

I realise it is not nice to contemplate having to take any medication for the rest of one’s life but at least it is just a pill a day and not 1 or 2 o 3 injections a day that is the bad luck for many diabetics.

Hard Arteries & Soft Bones

There is a known paradox that as the body ages there is a tendency for minerals to disappear from bone (osteoporosis) whilst, at the same time, increasing calcification is seen in blood vessels (atherosclerosis). However, in the absence of disease, the blood calcium levels remain remarkably constant despite wide variations in the amount of calcium ingested in both food and drink.

It is vital that the body maintains the concentration of calcium in the blood and ECF (extracellular fluid) within very narrow limits and it is very good at doing this. It has to be good at doing this because vital physiological actions (such as normal nerve conduction and all forms of muscle contraction) depend on the levels being very accurately set. Even quite small changes in blood calcium levels can have serious consequences for the whole nervous system and for the heart.

This finely tuned calcium homeostasis is achieved long-term by an ability to store excess in bone and also to excrete it in urine and faeces. When too little is ingested  the opposite happens – excretion is slowed  down and the blood level can be restored from the huge quantities stored in bone. Up until about the age of 25 the total amount stored in bone keeps rising. Thereafter this large store gradually falls, particularly in women after the menopause.

Other reasons than simply looking at calcium intake need to be found to explain the “calcium-out-of-bone and calcium-into-blood-vessel paradox”. Some yet unknown linking factor may yet come to light but for now these two contradictory effects would seem to be unrelated and not a paradox at all.

I need to say that I am not a specialist in the highly complex field of mineral metabolism though I used to be a specialist in Intensive Care and had to deal with the clinical consequences when such metabolism goes astray. It must be pointed out that soft tissues, other than blood vessels, can become calcified and that this can happen in both the young and the old. Leaving aside the formation of stones in urine, which can be understood by straightforward chemistry, there are numerous other examples of where calcification occurs in tumours, in bacterial nodules and other areas subject to chronic inflammation or irritation.

It is a straightforward postulate that the actual reason for “hardening of the arteries” is the chronic deposition therein of cholesterol-related plaques damaging the lining of the blood vessels and thence attracting calcification by attachment to adjacent Ca++ ions present in blood and the ECF of the the endothelium (the cellular lining) of the vessels. Also, and somewhat critically, that this will occur regardless of the blood calcium level. Such calcification in soft tissues is almost entirely a one way process with little or no reversal possible – unlike the active processes going on in bone formation and resorption.

Calcification takes place in the inner layer of arteries in the process known as atherosclerosis. The process begins with the  production of atheroma. This process, perhaps  surprisingly, begins in everyone in childhood and progresses at different rates in different individuals. Low density lipoproteins enter the inner endothelial layer of arteries and so do monocyte cells which then turn into macrophages. These phagocytic cells ingest these lipids. Some of the lipids can be exported to the liver by high density lipoproteins but the phagocytes eventually die and break apart leaving lipids and cell debris behind them. This is thus an inflammatory process and new macrophages then gobble up the mess and the process is repeated. Sequential calcification of these atheromatous plaques completes the process eventually leaving the vessels hard, inflexible, the lumen reduced in diameter and the whole vessel weakened both on the inside and on the outside. Sacs known as aneurysms (which can burst) may form on the outside and internal tears release substances which promote the formation of blood clots or thrombi. It is these thrombi that are the commonest cause of heart attacks and strokes.

Uncrystallised/dissolved calcium in the body fluids exists in two forms. As free chemically active calcium ions (Ca++) and also in another bound form where these cations (positively charged ions) are attached to corresponding (negatively charged) anions. Many of these bound anions will be chloride ions (Cl-) but the majority of bound calcium is tied to plasma proteins such as albumin. These proteins bind to Ca++ ions where they have negatively charged electrons available on their surface. These electronegative spots can also bind to any other available cations such as hydrogen (H+) and magnesium (Mg++) ions, all of which constantly compete with each other to pair up with any available electrons (e-).

It is most important to understand that it is the concentration of the unbound, free, ionised Ca++ ions that plays the critical role in the physiological reactions involving calcium in an organism. Any sudden change in the acid-base status, for example, is just one way of altering the bound to unbound ratio of the Ca++ ions since hydrogen (H+) ions constantly compete for their share of any available electrons. Thus if the blood becomes less acid (fewer H+ ions) some are then freed-up from where they had been bound to proteins in order to compensate for the induced alkalosis. The thus liberated  electronegative spots on the proteins can then be occupied by Ca++ ions causing a temporary fall in the free ionised levels of calcium. The resulting lowered ionised calcium levels (clinical hypocalcaemia) can rapidly cause symptoms such as tetany (muscle spasms) despite the fact that the body has enormous stores of calcium, in reserve, in its bone.

There is another closely related element, magnesium, that also plays a vital role in mineral metabolism. In like manner to calcium it dissociates into Mg++ ions and it too contributes to the large store of minerals in bone. Calcium and magnesium play intimately related roles, despite the fact that their clinical and physiological effects are often completely opposite to one another. It may seem surprising that atoms of calcium and magnesium (which are so similar both chemically and in size) can have such different effects. For now a simple approach is to say that when and where calcium levels cause excitement to nerves and muscles, magnesium tends to damp these effects down. Calcium does not exist in high concentrations inside cells, whereas magnesium is found there in significant amounts.

When a lot of people think of bone they imagine a hard, inflexible, dry and rather inert material. Nothing could be further from the truth. Living bone is a dynamic, flexible and metabolic tissue with a large blood supply. The fracture of a just a couple of large bones can lead to the need for a blood transfusion. In its marrow lie cells that are important in the formation of blood and for support of the immune system. When bones are broken they can, with certain limitations, rejoin and remould themselves. Bones are in fact constantly being dissolved and rebuilt. This is brought about respectively by osteoclasts and osteoblasts – two sets of very different specialised cells under hormonal control, which are capable of releasing and fixing calcium. Dissolving bone fairly obviously raises free calcium and rebuilding bone lowers it.

A very simple and classical overview of the hormonal control of calcium metabolism is that parathyroid hormone (PTH) corrects low levels and calcitonin (made in the thyroid) corrects high levels. These effects are mostly mediated by the control of osteoclast and osteoblast activity and by regulating renal excretion and reabsorption.

Vitamin D (or calciferol) in a number of forms plays an important ancillary role particularly where it can promote the absorption of calcium from the gut. Sub-optimal levels of vitamin D are particularly prevalent in the elderly and in northern latitudes or in those not exposed to enough sun. This can lead to a degree of secondary hyperparathyroidism (the release of PTH in response to lowered calcium levels) which in turn accentuates the demineralisation of bone so that blood levels of calcium are restored. A small daily intake of 400 to 800 IU is a straightforward, safe and inexpensive way to minimise this effect, particularly in the elderly. In postmenopausal women and in other conditions where there may be lower than normal levels of oestrogen (or testosterone in men) supplements of vitamin D will have little effect if the body’s levels are already OK but can help offset demineralisation if taken in conjunction with adequate calcium intake.

The complete picture of mineral metabolism is much, much more complicated than outlined so far. The relevant hormones and their co-factors interact in a complex manner. The interplay between calcium, magnesium, the acid-base status and other dissolved particles is equally complex. Low secretion of PTH, as just one example, can have the reverse effect of higher secretion. The fine control of the blood levels of these vital minerals and the mechanisms by which they affect their target cells (both directly and through various channels and gates in the cell membrane) is a very interesting subject but too big to consider right now. Newer research and understanding about this whole area may yet determine important roles for some of the vitamin K groups and a variety of other compounds such as the interleukins (which are involved in the production and control of osteoclasts).

A general overview of the body’s calcium stores is that, in youth and while the skeleton is still developing, a maximal store of calcium phosphate is created and laid down in bone in the form of the mineral hydroxyapatite (a type of calcium phosphate). Those that had a healthy youth and who have a big body frame get off to the best start. Thereafter there is gradual demineralisation of bone in just about everybody. One other noteworthy effect is that bones stay stronger when they bear weight. Being bedridden or being suspended in outer space or having one’s limbs immobilised in plaster are all examples that have detrimental effects on bone density. It is one area where a degree of obesity can actually be beneficial – perhaps this is because of the extra weight-bearing involved.

Suffice it to say that in the absence of disease and in the presence of a “normal” diet one is most unlikely to ever suffer the bad consequences of too much calcium or magnesium in the system. Eating and drinking adequate amounts of calcium and magnesium would actually seem to be sensible and not controversial. Taking small supplements of vitamin D (particularly for those not exposed to much sunlight or who are otherwise at risk of developing osteoporosis) has merit. There is increasing evidence that many (if not most) people do not consume enough magnesium and so perhaps, without overdoing it, regular supplements could have beneficial effects on maintaining not only an improved calcium status but also to give a bit of protection from some of the cardiovascular diseases that plague humanity now at the beginning of the third millennium.

Diet is one thing and it is so often regarded as the first port of call when things in one’s system seem to not be going to plan. For those truly interested in their health I would simply ask that, rather than concentrating on their diets, they concentrated on their whole lifestyle. Both smoking and excessive alcohol intake have a negative effect on bone mineralisation. Smoking puts people at a real risk of heart attack or stroke and a sedentary life will only exacerbate all these problems. I will not lecture others on what they should or should not do so, in return, please don’t lecture me.

I intend to write about my views on “diets” elsewhere but let me also say that I am not a health saint. I have always drunk a certain amount of alcohol and I smoked pretty heavily between the ages of 28 and 55. I was not overweight, not diabetic, my total cholesterol was normal, my blood pressure was normal, I was active on my farm and unstressed mentally and then one night I had a heart attack. I can certainly say that it was a shock and that I was very lucky that it was small and posterior (at the back of the heart) and very rapidly treated with “clot-busters” and a stent. As I lay in the Mater Hospital in Dublin, watching the radiologist doing the angiography and admiring his skill, I was able to see where a plaque of cholesterol had torn the lining of the artery. At that moment I also realised that about the only known risk factor in my life was that I was a smoker. So I determined, there and then, that I would never smoke again. I never did and I was never even tempted to begin.

Others can fool themselves if they want to and (just as I had done many times before) make periodic attempts to stop smoking or simply not care at all. With hindsight I know these two things. The first is to never even be tempted to start smoking – it is as easy (or easier) to become addicted to cigarettes as to heroin and for this the manufacturers and suppliers have to bear a share of the blame. The second point is that when I had tried to stop smoking, on a number of occasions, it was always in a rather “hopeful” way but that when I did finally stop it was because I had made a definite decision to do so. So you can do it if you want to but I believe you will be unlikely to succeed unless you make it your own conscious and definitive decision. A decision no one can take away from you.

I know I have already digressed away from mineral metabolism but while it is still in my mind I would like to add that the reason I started smoking tobacco was actually because I was tempted to try that “harmless” drug marijuana when at university in the 70s. I never became a regular user of the stuff and for me it was never (and was never likely to become) a “gateway” drug to heroin, cocaine, etc but it did lead me very quickly to an addiction to cigarettes. Be warned.